Jiang Qian, Xu Mengmeng, Chen Hong, Zhang Yao, Sun Yuting, Tao Li, Wang Zheng, Yang Deqin
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, 404100, Chongqing, China.
Department of Conservative Dentistry and Endodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China.
NPJ Biofilms Microbiomes. 2025 Mar 8;11(1):41. doi: 10.1038/s41522-025-00660-7.
The interaction between Candida albicans and Streptococcus mutans plays an important role in the progression of dental caries. The vacuolar proton pump (V-ATPase) is a vital enzyme regulating the growth and virulence of C. albicans, which is a potential target for caries prevention. However, the effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm remains to be explored. In this study, the detection rate of C. albicans in caries-active (group CA) (22.03%) was significantly higher than that in caries-free (group CF) children (8.00%), and the expression of V-ATPase related genes were higher in group CA. Then, the higher expressed V-ATPase coding genes VMA3, VMA4 and VMA11 in CA group were knocked out. Compared with the wild type SC5314, the mutants showed slower growth rate, inhibited hyphal growth, and defective integrity of cell wall. The biofilm biomass and extracellular polysaccharide (EPS) production of dual biofilm were significantly reduced, and the biofilm structure was impacted. Transcriptome analysis indicated that V-ATPase participated in various metabolisms and biosynthesis pathways of C. albicans, and influenced EPS metabolism of S. mutans. Finally, compared with the positive control, the caries severity, the biomass and EPS production of dental plaque were significantly reduced after deletion of VMA3, VMA4 and VMA11 in vivo. This study revealed for the first time the regulating effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm and its potential mechanisms. The results may provide basis for new strategies of ecological prevention and treatment of dental caries.
白色念珠菌与变形链球菌之间的相互作用在龋齿进展中起重要作用。液泡质子泵（V-ATP酶）是调节白色念珠菌生长和毒力的重要酶，是预防龋齿的潜在靶点。然而，V-ATP酶对白色念珠菌-变形链球菌生物膜致龋性的影响仍有待探索。本研究中，患龋活跃儿童组（CA组）白色念珠菌检出率（22.03%）显著高于无龋儿童组（CF组）（8.00%），且CA组V-ATP酶相关基因表达更高。然后，敲除CA组中表达较高的V-ATP酶编码基因VMA3、VMA4和VMA11。与野生型SC5314相比，突变体生长速率减慢，菌丝生长受抑制，细胞壁完整性受损。双菌生物膜的生物膜生物量和胞外多糖（EPS）产量显著降低，生物膜结构受到影响。转录组分析表明，V-ATP酶参与白色念珠菌的多种代谢和生物合成途径，并影响变形链球菌的EPS代谢。最后，与阳性对照相比，体内敲除VMA3、VMA4和VMA11后，龋齿严重程度、牙菌斑生物量和EPS产量显著降低。本研究首次揭示了V-ATP酶对白色念珠菌-变形链球菌生物膜致龋性的调节作用及其潜在机制。研究结果可为龋齿生态防治新策略提供依据。
